Molecular Markers of Neuroplasticity During Exercise in People With Incomplete Spinal Cord Injury

NCT01538693 | Completed

• 1 other identifier: STU00056144
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether exercising (walking) at different intensities increases levels of factors in the blood and saliva that are known to impact neuroplasticity (how the connections in the spinal cord and brain can change) and if these levels are changed by pairing exercise with a single dose of commonly used prescription drugs or by your mood.

Conditions

Spinal Cord Injury

Keywords

BDNF; serotonin; high-intensity; exercise

Outcome Measures

Primary Outcomes (1)

• Change in blood serum concentration of neuroplastic proteins

  During a graded treadmill test, 5mL of blood will be taken at each speed the subject is able to obtain before failure. 5mL of blood will also be taken immediately after completion of the treadmill test and every 10 minutes for up to 30 minutes after completion.

  assessed prior to, throughout, and following the duration of a graded exercise test, over an expected average of 2 hours

Secondary Outcomes (11)

• fastest possible walking velocity overground

  one time, baseline measure

• Six Minute Walk Distance

  one time basline measurement

• Volitional strength: Lower Extremity Motor Score

  one time baseline measure

• Modified Ashworth Scale

  one time baseline measurement

• Spinal Cord Assessment tool for Spasticity

  one time baseline measure

Study Arms (3)

escitalopram oxalate

ACTIVE COMPARATOR

Exercise testing with escitalopram oxalate dose

Drug: escitalopram oxalate; Other: Graded intensity exercise

cyproheptadine

ACTIVE COMPARATOR

exercise testing with cyproheptadine dose

Drug: Cyproheptadine; Other: Graded intensity exercise

placebo

PLACEBO COMPARATOR

exercise testing with placebo dose

Drug: sugar pill; Other: Graded intensity exercise

Interventions

escitalopram oxalate DRUG

10 mg 4.5 hours prior to testing

Also known as: Lexapro

escitalopram oxalate

Cyproheptadine DRUG

8mg 4.5 hours prior to testing

cyproheptadine

sugar pill DRUG

4.5 hour prior to testing

placebo

Graded intensity exercise OTHER

modified bruce protocol for peak oxygen consumption testing

cyproheptadine; escitalopram oxalate; placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be motor incomplete spinal cord injury (ASIA C or D) of 1 year or greater duration, with anatomical lesions between C1-T10
• Must be between 18 and 75 years of age
• Must be ambulatory with passive range of motion consistent with normal walking, and must include: ankle dorsiflexion ankle to 10° and plantarflexion to 30°, knee flexion from 0 to 90°, hip flexion/extension to 90° to -10°.
• Must be medically stable with medical clearance to participate, with absence of concurrent severe medical illness including: unhealed decubiti, existing infection, significant cardiovascular or metabolic disease which limits exercise participation, significant osteoporosis (as indicated by history of fractures following injury), active heterotrophic ossification in the lower extremities, known history of peripheral nerve injury in lower legs, history of known traumatic head injury, mental illness, history of pre-existing QT interval prolongation, congenital long QT syndrome, and history of pulmonary complications, including significant obstructive and/or restrictive lung diseases
• May be undergoing concurrent physical therapy
• May be of childbearing potential (for women)
• Men and women will be recruited for participation in the proposed study at rates consistent with national and local average of gender disparities of SCI (80% male, 20% women)
• Individuals of different ethnicities will be recruited at rates similar to the national and local ethnicity rates. Current data since 2005 indicate that of the entire population of SCI, 66.1% are Caucasian, 27.1% are African American, 6.6% are of Hispanic origin, and 2.0% are Asian.

You may not qualify if:

• Weighing more than 300lbs
• Ventilator-dependency
• Use of substantial orthopedic bracing to stabilize the cervical or thoracic vertebral column
• Inability to tolerate 10 minutes of standing without orthostasis (decrease in blood pressure by 20 mmHg systolic and 10 mmHg diastolic).
• Women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the pharmacological agents on the developing fetus
• Exhibiting symptoms suggestive of depression according to the Personal health Questionaire (PHQ-9)
• Subjects who exhibit hemoglobin levels consistent with anemia (\<13g/dL for men and \<12g/dL for women) will be excluded from the study.
• Currently taking prescribed anti-depressant medications, including specific monoaminergic agents, their precursors or their agonists, antipsychotics, medications known to prolong the QT interval, or other medications with known interactions to the SSRIs. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 14-day washout period for SSRIs and a 72 hour washout for Tizanidine will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
• Currently taking prescribed anti-spastic medications. Specific agents to be excluded include baclofen (Lioresal®) and benzodiazepines (Diazepam®). Selected agents used for pain modulation will be evaluated per subject to ascertain potential interactions with test agent. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 72-hour minimum washout period for all such medications will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
• Clinically diagnosed liver, renal, or other metabolic disease that may interfere with drug action and/or clearance

Sponsors & Collaborators

• T. George Hornby: lead
• University of Medicine and Dentistry of New Jersey: collaborator
• Shirley Ryan AbilityLab: collaborator

Study Sites (1)

Rehabiliation Institute of Chicago

Chicago, Illinois, 60611, United States

Location

Related Publications (15)

• Ying Z, Roy RR, Zhong H, Zdunowski S, Edgerton VR, Gomez-Pinilla F. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuroscience. 2008 Sep 9;155(4):1070-8. doi: 10.1016/j.neuroscience.2008.06.057. Epub 2008 Jul 3.

  PMID: 18672032 BACKGROUND

• Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol. 2005 Jun;193(2):411-9. doi: 10.1016/j.expneurol.2005.01.015.

  PMID: 15869943 BACKGROUND

• Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. 2010 Sep 1;40(9):765-801. doi: 10.2165/11534530-000000000-00000.

  PMID: 20726622 BACKGROUND

• Ferris LT, Williams JS, Shen CL. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc. 2007 Apr;39(4):728-34. doi: 10.1249/mss.0b013e31802f04c7.

  PMID: 17414812 BACKGROUND

• Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002 Jun;25(6):295-301. doi: 10.1016/s0166-2236(02)02143-4.

  PMID: 12086747 BACKGROUND

• Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996 Jul 8;726(1-2):49-56.

  PMID: 8836544 BACKGROUND

• Ivy AS, Rodriguez FG, Garcia C, Chen MJ, Russo-Neustadt AA. Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacol Biochem Behav. 2003 Apr;75(1):81-8. doi: 10.1016/s0091-3057(03)00044-3.

  PMID: 12759116 BACKGROUND

• Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995 Nov;15(11):7539-47. doi: 10.1523/JNEUROSCI.15-11-07539.1995.

  PMID: 7472505 BACKGROUND

• Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW. Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience. 2000;101(2):305-12. doi: 10.1016/s0306-4522(00)00349-3.

  PMID: 11074154 BACKGROUND

• Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology. 1999 Nov;21(5):679-82. doi: 10.1016/S0893-133X(99)00059-7.

  PMID: 10516964 BACKGROUND

• Garcia C, Chen MJ, Garza AA, Cotman CW, Russo-Neustadt A. The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity. Neuroscience. 2003;119(3):721-32. doi: 10.1016/s0306-4522(03)00192-1.

  PMID: 12809693 BACKGROUND

• Pearson-Fuhrhop KM, Cramer SC. Genetic influences on neural plasticity. PM R. 2010 Dec;2(12 Suppl 2):S227-40. doi: 10.1016/j.pmrj.2010.09.011.

  PMID: 21172685 BACKGROUND

• Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M, Houlden H, Bhatia K, Greenwood R, Rothwell JC. A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J Physiol. 2008 Dec 1;586(23):5717-25. doi: 10.1113/jphysiol.2008.159905. Epub 2008 Oct 9.

  PMID: 18845611 BACKGROUND

• Bryan A, Hutchison KE, Seals DR, Allen DL. A transdisciplinary model integrating genetic, physiological, and psychological correlates of voluntary exercise. Health Psychol. 2007 Jan;26(1):30-9. doi: 10.1037/0278-6133.26.1.30.

  PMID: 17209695 BACKGROUND

• Mata J, Thompson RJ, Gotlib IH. BDNF genotype moderates the relation between physical activity and depressive symptoms. Health Psychol. 2010 Mar;29(2):130-3. doi: 10.1037/a0017261.

  PMID: 20230085 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Motor Activity

Interventions

Escitalopram; Cyproheptadine; Sugars

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Polycyclic Compounds; Carbohydrates

Study Officials

• Thomas G Hornby, PhD, PT

  University of Illinois at Chicago, Rehabiliation Institute of Chicago, Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: February 24, 2012
• Study Start: December 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

US (1)